Longitudinal immune profiling of SARS-CoV-2 reinfection in solid organ transplant recipient

  

View ORCID ProfileJonathan Klein,  View ORCID ProfileAnderson F. Brito, Paul Trubin, Peiwen Lu, Patrick Wong, Tara Alpert, Mario A. Pena-Hernandez, Winston Haynes, Kathy Kamath, Feimei Liu, Chantal B.F. Vogels, Joseph R. Fauver, Carolina Lucas, Jieun Oh, Tianyang Mao, Julio Silva, Anne L. Wyllie, Catherine Muenker, Arnau Casanovas-Massana, Adam J. Moore, Mary E. Petrone, Chaney C. Kalinich, IMPACT Research Team, Charles Dela Cruz, Shelli Farhadian, Aaron Ring, John Shon, Albert I. Ko, Nathan D. Grubaugh, Benjamin Israelow,  View ORCID ProfileAkiko Iwasaki, Marwan M. Azar

doi: https://doi.org/10.1101/2021.03.24.21253992

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.03.24.21253992v1.full.pdf

Abstract

Prior to the emergence of antigenically distinct SARS-CoV-2 variants, reinfections were reported infrequently - presumably due to the generation of durable and protective immune responses. However, case reports also suggested that rare, repeated infections may occur as soon as 48 days following initial disease onset. The underlying immunologic deficiencies enabling SARS-CoV-2 reinfections are currently unknown. Here we describe a renal transplant recipient who developed recurrent, symptomatic SARS-CoV-2 infection - confirmed by whole virus genome sequencing - 7 months after primary infection. To elucidate the immunological mechanisms responsible for SARS-CoV-2 reinfection, we performed longitudinal profiling of cellular and humoral responses during both primary and recurrent SARS-CoV-2 infection. We found that the patient responded to the primary infection with transient, poor-quality adaptive immune responses. The patients immune system was further compromised by intervening treatment for acute rejection of the renal allograft prior to reinfection. Importantly, we also identified the development of neutralizing antibodies and the formation of humoral memory responses prior to SARS-CoV-2 reinfection. However, these neutralizing antibodies failed to confer protection against reinfection, suggesting that additional factors are required for efficient prevention of SARS-CoV-2 reinfection. Further, we found no evidence supporting viral evasion of primary adaptive immune responses, suggesting that susceptibility to reinfection may be determined by host factors rather than pathogen adaptation in this patient. In summary, our study suggests that a low neutralizing antibody presence alone is not sufficient to confer resistance against reinfection. Thus, patients with solid organ transplantation, or patients who are otherwise immunosuppressed, who recover from infection with SARS-CoV-2 may not develop sufficient protective immunity and are at risk of reinfection.

Competing Interest Statement

AI served as a consultant for Spring Discovery, Boehringer Ingelheim, and Adaptive Biotechnologies.

Funding Statement

This work was supported by the Womens Health Research at Yale Pilot Project Program (A.I.), Fast Grant from Emergent Ventures at the Mercatus Center (A.I. and N.D.G), Mathers Foundation, the Ludwig Family Foundation, the Department of Internal Medicine at the Yale School of Medicine, Yale School of Public Health, the Beatrice Kleinberg Neuwirth Fund, and CDC Contract # 75D30120C09570 (N.D.G.). IMPACT received support from the Yale COVID-19 Research Resource Fund. A.I. is an Investigator of the Howard Hughes Medical Institute. J.K. received support from NIH T32 MSTP training grant. B.I received support from NIAID 2T32AI007517-16. T.A. and M.E.P were supported by CTSA Grant Number TL1 TR001864.

https://www.medrxiv.org/content/10.1101/2021.03.24.21253992v1